Lunze K, Gilbert N, Mebus S, Miera O, Fehske W, Uhlemann F, Mühler E G, Ewert P, Lange P E, Berger F, Schulze-Neick I
Klinik für angeborene Herzfehler/Kinderkardiologie, Deutsches Herzzentrum Berlin, Berlin, Germany.
Eur J Clin Invest. 2006 Sep;36 Suppl 3:32-8. doi: 10.1111/j.1365-2362.2006.01692.x.
New oral substances such as beraprost, bosentan and sildenafil have proven effective in different forms of pulmonary arterial hypertension (PAH), both alone and in combination with standard treatment such as intravenous and inhaled prostacyclins. However, there are few reports so far on the effect of a combination of exclusively oral substances. In this paper, we present our initial findings of treatment using a combination of these oral substances in a heterogeneous group of patients with different forms of PAH.
Eleven patients with a median age of 12.9 years (5.5-54.7 years) with both idiopathic PAH and forms associated with congenital cardiac defects (PAH-CHD) with a mean pulmonary arterial pressure > 25 mmHg were enrolled in an observational, open-label, prospective, single-centre study. Either combination treatment with bosentan and sildenafil was started initially, or an existing bosentan treatment was complemented with sildenafil given as an add-on therapy. Mean doses given were 2.3 +/- 0.6 mg kg(-1) for bosentan and 2.1 +/- 0.9 mg kg(-1) for sildenafil. Clinical status, exercise capacity, and haemodynamics were assessed at baseline and at the end of the observation period after a mean follow-up time of 1.1 years (0.5-2.5 years).
No major side effects regarding liver function and blood pressure regulation were noted. One patient died of sudden death elsewhere. Most patients were in New York Heart Association (NYHA) functional class III. Clinical improvement was about one NYHA class (mean 2.8 +/- 0.4-1.6 +/- 0.8, P = 0.001), which was associated with an increase of transcutaneous oxygen saturation (89.9 +/- 9.9-92.3 +/- 7.1%; P = 0.037), maximum oxygen uptake (18.1 +/- 6.8-22.8 +/- 10.4 mL kg(-1) x min; P = 0.043), and 6-minute walking distance (351 +/- 58-451 +/- 119 m; P = 0.039). Mean pulmonary arterial pressure measured invasively decreased (62 +/- 12-46 +/- 18 mmHg; P = 0.041).
In our patient group, a combination of oral bosentan and sildenafil proved to be safe and effective. Clearly, randomized, double-blind, placebo-controlled studies are warranted to define the role and type of combination therapies in PAH.
新型口服药物如贝前列素、波生坦和西地那非已被证明在不同类型的肺动脉高压（PAH）中单独使用或与静脉内和吸入性前列环素等标准治疗联合使用时均有效。然而，目前关于仅口服药物联合使用效果的报道较少。在本文中，我们展示了在一组不同类型PAH的异质性患者中使用这些口服药物联合治疗的初步结果。
11名年龄中位数为12.9岁（5.5 - 54.7岁）的特发性PAH患者以及与先天性心脏缺陷相关的PAH（PAH-CHD）患者，其平均肺动脉压>25 mmHg，纳入了一项观察性、开放标签、前瞻性、单中心研究。最初要么开始使用波生坦和西地那非联合治疗，要么在现有的波生坦治疗基础上加用西地那非作为附加治疗。波生坦的平均剂量为2.3±0.6 mg·kg⁻¹，西地那非的平均剂量为2.1±0.9 mg·kg⁻¹。在基线和平均随访1.1年（0.5 - 2.5年）后的观察期结束时评估临床状态、运动能力和血流动力学。
未发现关于肝功能和血压调节的重大副作用。一名患者在其他地方猝死。大多数患者处于纽约心脏协会（NYHA）功能分级III级。临床改善约为一个NYHA分级（平均2.8±0.4 - 1.6±0.8，P = 0.001），这与经皮血氧饱和度增加（89.9±9.9 - 9
